title: Synthesis, structure, and activities of an oral mucosal alpha-defensin from rhesus macaque.
abstract: The oral cavity is an environment challenged by a large variety of pathogens. Consequently, the antimicrobial peptides expressed in that environment are interesting as they evolved to defend against a broad spectrum of bacteria and fungi. Here we report the discovery of new alpha-defensins from rhesus macaque oral mucosa and determine the first alpha-defensin structure from that species. The new peptides were identified by sequencing of reverse transcriptase-PCR products obtained from oral mucosal tissues, disclosing three mucosal alpha-defensins, termed rhesus macaque oral alpha-defensins (ROADs). The peptide corresponding to fully processed ROAD-1 was synthesized, subjected to folding/oxidation conditions, and purified. ROAD-1 was active against Staphylococcus aureus, Escherichia coli, and Candida albicans in a concentration-dependent manner. We determined the structure of ROAD-1 using NMR spectroscopy and find that the synthetic peptide adopts the canonical disulfide pairing and alpha-defensin fold. The antimicrobial mechanism of defensins has been correlated with their ability to disrupt and permeabilize the cell envelope, activities that depend on the surface features of the folded peptide. Although ROAD-1 maintains the defensin fold, the oral defensin displays distinct surface features when compared with other alpha-defensin structures.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA.
authors.forename: Sheeja
authors.initials: S
authors.lastname: Vasudevan
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: George
authors.initials: G
authors.lastname: Osapay
authors.forename: Patti
authors.initials: P
authors.lastname: Tran
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tai
authors.forename: Warren
authors.initials: W
authors.lastname: Liang
authors.forename: Vasanth
authors.initials: V
authors.lastname: Kumar
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selsted
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Cocco
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology*; D002176:Candida albicans / Q000254:growth & development*; D004926:Escherichia coli / Q000254:growth & development*; D008253:Macaca mulatta; D009061:Mouth Mucosa / Q000276:immunology; D017510:Protein Folding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000254:growth & development*; D013329:Structure-Activity Relationship; D023084:alpha-Defensins / Q000138:chemical synthesis / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D023084:alpha-Defensins